To measure the effect of DAe and the DA surge on the quantitation of DA receptor density using NMSP and RAC. Using amphetamine (AMP) and reserpine (RES), which, respectively, increases or decreases DAe, we will perturb the DA system. We will then measure the effects of these perturbations on DA D2 receptors ("D2-like"). Progress is to examine the effects of endogenous dopamine on the quantification of absolute receptor density Bmax with [11C]raclopride and [11C]NMSP. To date, we have successfully completed eight normal subjects and four schizophrenic patients with two measurements of Bmax without and with amphetamine. Since each Bmax measurement requires both high and low specific activity [11C]raclopride, each subject received four PET scans over a period of 1-2 weeks. This is logistically a complex procedure, since in the case of the patients, they must remain drug-free between the pairs of PET scans, each pair of which are carried out on a single day. This has often required hospitalization in the Clinical Research Unit at Johns Hopkins. In some cases, for clinical reasons, it has been necessary to enter subjects into a two PET scan protocol only, with two high specific activity [11C]raclopride studies without and with amphetamine during the same day. This has occurred in one of the six patients recruited so far. The effect of amphetamine is to cause a fall in the observed Bmax. The average fall in Bmax is greater in schizophrenic patients (2 to 3 fold) but the variance is very large in patients and normals. With methods refinement, more subtyping and expanded samples these results may achieve statistical significance.